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Customized Multilayered Tissue-on-a-Chip (MToC) to Simulate Bacillus Calmette–Guérin (BCG) Immunotherapy for Bladder Cancer Treatment

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Abstract

As an advanced cell culture platform, the organ-on-a-chip has been in the spotlight recently owing to its ability to maintain the physiological characteristics of cells in vitro. Therefore, several disease models have been developed using the organ-on-a-chip technology, and the organ specific three-dimensional (3D) structure and various mechanical/chemical stimuli built into the chip enable efficient development of drugs, medical devices, and biomaterials, as well as realization of patient-specific precise medicine. This study introduces a novel chip-based non-muscle invasive bladder cancer model, multilayered tissue-on-a-chip (MToC), which was created using 3D bio-printing technology, micro-milling, and soft lithography based polydimethylsiloxane (PDMS) casting. All types of cells, T24, MRC-5, and HUVEC, were successfully co-cultured in the MToC. Using computational fluid dynamics (CFD), the flow phenomena occurring in MToC were analyzed. Further, we attempted Bacillus Calmette–Guérin (BCG)-induced migration of THP-1, and the viability reduction of bladder cancer cells and the THP-1 migration were observed. Although follow-up studies are needed to precisely mimic the immune response, this partial phenomenon of the immune response suggests the potential of this device as a surrogate experimental tool for BCG immunotherapy in future.

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Acknowledgements

This research was supported by the National Research Foundation (NRF) of the Republic of Korea (NRF-2018R1D1A1A02050248 and NRF-2021R1A2C1004307 to IHC), the Basic Science Research Program (2019R1F1A1062123 to JYP), and the Bio & Medical Technology Development Program (2018M3A9H1023141 to JYP) of the NRF funded by the Korean government, MSIT.

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Author notes

  1. Seungjin Lee and Jung Hoon Kim contributed equally to this work.

  2. In Ho Chang and Joong Yull Park contributed equally to this work

Authors and Affiliations

  1. School of Mechanical Engineering, College of Engineering, Chung-Ang University, Seoul, 06974, Republic of Korea

    Seungjin Lee & Joong Yull Park

  2. Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, 06973, Republic of Korea

    Jung Hoon Kim, Su Jeong Kang & In Ho Chang

  3. Department of Intelligent Energy and Industry, Graduate School, Chung-Ang University, Seoul, 06974, Republic of Korea

    Joong Yull Park

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  1. Seungjin Lee
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Correspondence to Joong Yull Park.

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Lee, S., Kim, J.H., Kang, S.J. et al. Customized Multilayered Tissue-on-a-Chip (MToC) to Simulate Bacillus Calmette–Guérin (BCG) Immunotherapy for Bladder Cancer Treatment. BioChip J 16, 67–81 (2022). https://doi.org/10.1007/s13206-022-00047-2

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  • DOI: https://doi.org/10.1007/s13206-022-00047-2

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